EBMT 2019 | Autologous fecal microbiota transfer is safe and effective in patients with AML: results from the ODYSSEE trial

Loss of microbiota diversity after high-dose chemotherapy has often been linked with complications, such as infections, poor nutritional status, longer hospitalization, as well as disruptions to therapy as a result of toxicity.¹ On 27 March 2019, at the 45^th Annual Meeting of the European Society for Blood and Marrow Transplantation, Professor Florent Malard, a member of our GvHD Hub Steering Committee, presented results from the ODYSSEE study.²

Professor Malard discussed the potential complications which may arise as a result of a loss of microbiota diversity which includes infectious complications, poor nutritional status, longer hospitalization, as well as disruptions to therapy due to toxicity.³ The ODYSSEE study (NCT02928523) examined the effect of autologous fecal microbiota transfer (auto-FMT) on the recovery of microbiota diversity in consecutive adult patients with de-novo AML or high-risk myelodysplastic syndrome (HR MDS; n = 25) receiving prior intensive induction chemotherapy and antibiotic therapy, and follow-up with consolidation chemotherapy.²

Key findings:

Efficacy

• Patients (n = 25) received auto-FMT after induction chemotherapy followed by antibiotic prophylaxis (time-point V2)
• Patients analyzed in the per-protocol population (n = 20; median age = 50 years; range, 24–68) received induction chemotherapy with:
  • Cytarabine and daunorubicin: 35% (n = 7)
  • Cytarabine and idarubicin: 60% (n = 12)
  • Other: 5% (n = 1)
• At time-point V2, a severe reduction in microbiome diversity was seen with a domination of pro-inflammatory enterococcus strains and high levels of the inflammatory markers neopterin and C-reactive protein
• At time-point V3 (10 days after auto-FMT and before consolidation therapy) baseline microbiome diversity was restored to > 90% of pre-therapy levels (time-point V1)
• In addition, there was a reduction in antibiotic resistant gene copy count between time-point V2 and V3 by 43%, and a reduction in neopterin (89.6%) and C-reactive protein (85.2%) levels
• One-year overall survival: 84%

Safety

• Within 30 days after auto-FMT, no serious adverse events (SAEs) were reported
• No adverse inflammatory reaction was induced by auto-FMT
• On study deaths: 4
  • None were reported to be related to auto-FMT
  • Median time to death from second dosing: 182.5 days (range, 113–225)

Professor Malard concluded that auto-FMT is an effective and safe regimen, which is able to restore microbial diversity following intensive induction chemotherapy in patients with AML. This finding may help patients to experience reduced complications during high-dose chemotherapy and antibiotic treatment.